He will semi-randomly switch between hopping towards the player, spitting a burst of blood shots (signified by smiling), or launch into the air and land at the spot the player was standing in when he went up along with blood shots fired in many directions when he hits the ground.
The distance between Isaac and Monstro will not influence the attack he will choose, he switches between them at will. Therefore, you'll want to stay at medium range to retain maximum flexibility. The blood shot spray looks nasty, but the shots have arcs that often go over your head.
It's also possible to circle around Monstro while staying at a short distance. This way, you don't have to worry about his shots, but his small leaps become a bit more dangerous.
Despite his bulk, Monstro moves around a fair bit; area of effect items (like Mr. Boom, Lemon Mishap, or Doctor's Remote) will not be very effective unless you get lucky on placement. Doctor's Remote, however, works somewhat well as you can use mouse clicks to stay on target with Monstro. Try to wait until he launches into the air, then move and aim where you were standing when he lept. Use his shadow to track where he will land.
Regular bombs take large chunks out of his health, but if he decides to launch you may end up wasting the bomb. An easy way to use area of effect items is when Monstro makes a huge jump, he will land approximately at your last position before he jumped, so just use the item before moving.
If you're down to one heart, avoiding damage becomes a number-one priority as some of his shots (the bigger ones) can deal up to a full heart of damage.
For some people it's hard to tell where he is when jumping in the air, so homing shots can help to predict his landing. You can sometimes tell by the shadow that his body makes in where he will land, but mainly, he only lands where your current position was/is
It's possible to run underneath Monstro while he is "hopping". This can make shooting a bit easier.
Pay attention. If Monstro uses his blood spray while you are cornered, look for an opening. There's an opening in every barrage he throws at you, so use this to your advantage.
Red Monstro is much smaller and has less health. An additional Monstro shows up, and you'll have to battle both of them simultaneously. In boss rooms, there will be two and in normal rooms in later levels, one will be added to the amount that would spawn in the room by default. Obviously, when smaller, it's harder to stay still and maintain fire, and with two or three of them present, it's best to run in a circle around them and never fully stop moving unless they're both just hopping around.
Gray Monstro is slightly larger and has more health. He can't launch himself into the air, and uses his shot attacks much more often.
Eternal Monstro appears larger, moves and attacks twice as fast and shoots more projectiles. It's capable to "duplicate" - split into 2 half-sized Eternal Monstros once 1/2 of its health is taken away. The same thing can also apply to those smaller Eternal Monstros, causing them to split again and become 1/4-sized. It's possible to make one Eternal Monstro split into a maximum of 4 small Eternal Monstros in one room. Half-sized Eternal Monstro acts the same as normal Monstro, and the 1/4-sized Eternal Monstro acts like the Grey variant.
If the 2 half-sized Eternal Monstros are killed simultaneously, each of them will spawn 3 smaller Eternal Monstros.
If Eternal Monstro is killed by II - The High Priestess, it won't split and count as a normal boss kill, which means no Eternal Hearts will be dropped if Eternal Monstro is killed in this way.
It is possible to have Monstro shove you out of the boss room. If he lands on you when you are next to the boss door, you can sometimes clip through it. This was later fixed upon release of the Wrath of the Lamb DLC.